Impaired vascular contractility and blood pressure homeostasis in the smooth muscle α‐actin null mouse

Abstract

The smooth muscle (SM) α‐actin gene activated during the early stages of embryonic cardiovascular development is switched off in late stage heart tissue and replaced by cardiac and skeletal α‐actins. SM α‐actin also appears during vascular development, but becomes the single most abundant protein in adult vascular smooth muscle cells. Tissue‐specific expression of SM α‐actin is thought to be required for the principal force‐generating capacity of the vascular smooth muscle cell. We wanted to determine whether SM α‐actin gene expression actually relates to an actin isoform's function. Analysis of SM α‐actin null mice indicated that SM α‐actin is not required for the formation of the cardiovascular system. Also, SM α‐actin null mice appeared to have no difficulty feeding or reproducing. Survival in the absence of SM α‐actin may result from other actin isoforms partially substituting for this isoform. In fact, skeletal α‐actin gene, an actin isoform not usually expressed in vascular smooth muscle, was activated in the aortas of these SM α‐actin null mice. However, even with a modest increase in skeletal α‐actin activity, highly compromised vascular contractility, tone, and blood flow were detected in SM α‐actin‐defective mice. This study supports the concept that SM α‐actin has a central role in regulating vascular contractility and blood pressure homeostasis, but is not required for the formation of the cardiovascular system.—Schildmeyer, L. A., Braun, R., Taffet, G., DeBiasi, M., Burns, A. E., Bradley, A., and Schwartz, R. J. Impaired vascular contractility and blood pressure homeostasis in the smooth muscle α‐actin null mouse. FASEB J. 14, 2213–2220 (2000)